Synthesis, Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors.

We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low-nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor-associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor-bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.

Assessment of human telomeric G-quadruplex structures using surface-enhanced Raman spectroscopy.

G-Quadruplex (G4) structures of a human telomeric 24-mer (5'-TTAGGGTTAGGGTTAGGGTTAGGG-3') sequence (Tel24) stabilized by sodium and potassium ions have been assessed using surface-enhanced Raman scattering (SERS) spectroscopy. The distinctive SERS spectra of Tel24 in the presence of 100 mM Na+ and 100 mM K+ were obtained and the SERS bands characteristic of the antiparallel basket-type and the mixed hybrid (3+1) structures, respectively, were identified and assigned. The influence of the SERS - active substrate on the scattering enhancement was studied using citrate- and chloride-covered silver nanoparticles, in the absence and presence of the aggregating agent (0.1 M Na2SO4 and 0.1 M K2SO4). The highly reproducible SERS spectra of Tel24 obtained in various SERS active media indicated the same adsorption mechanism of the cation - stabilized G-quadruplexes onto the metal surface, regardless of the silver colloid. The remarkable resemblance between the circular dichroism (CD) spectra of the Tel24 structures with and without the colloid confirmed that interaction with the enhancing silver surface did not affect the stability of the formed G4 structures. The presented study pointed to a great potential of the SERS spectroscopy for the sensitive structural analysis of various G4 topologies. Graphical Abstract SERS spectroscopy allowed identification of Na+ stabilized antiparallel basket-type and K+ stabilized hybrid (3+1) structures of the same 24-mer human telomeric sequence.